Katla Sai Krishna

Gold–silica quantum rattles for multimodal imaging and therapy

Significance Therapeutic and diagnostic nanoparticles combine multiple functionalities to improve efficacy of treatment but often require assembling complex systems at the expense of overall performance. Here we present a simple strategy to synthesize a hybrid, rattle-like, gold–silica nanoparticle that very efficiently combines therapy and imaging in an animal model. The nanoparticle design is uniquely centered on enabling the use of gold quantum dots (<2 nm) in biological systems. The resulting nanoparticles are highly biocompatible and display emergent photonic and magnetic properties matching and in some instances outperforming state-of-the-art nanotechnology-based medical agents for each of the functionalities investigated, promising a tighter integration between imaging and therapy. Gold quantum dots exhibit distinctive optical and magnetic behaviors compared with larger gold nanoparticles. However, their unfavorable interaction with living systems and lack of stability in aqueous solvents has so far prevented their adoption in biology and medicine. Here, a simple synthetic pathway integrates gold quantum dots within a mesoporous silica shell, alongside larger gold nanoparticles within the shell’s central cavity. This “quantum rattle” structure is stable in aqueous solutions, does not elicit cell toxicity, preserves the attractive near-infrared photonics and paramagnetism of gold quantum dots, and enhances the drug-carrier performance of the silica shell. In vivo, the quantum rattles reduced tumor burden in a single course of photothermal therapy while coupling three complementary imaging modalities: near-infrared fluorescence, photoacoustic, and magnetic resonance imaging. The incorporation of gold within the quantum rattles significantly enhanced the drug-carrier performance of the silica shell. This innovative material design based on the mutually beneficial interaction of gold and silica introduces the use of gold quantum dots for imaging and therapeutic applications.

Lab-on-a-chip synthesis of inorganic nanomaterials and quantum dots for biomedical applications.

The past two decades have seen a dramatic raise in the number of investigations leading to the development of Lab-on-a-Chip (LOC) devices for synthesis of nanomaterials. A majority of these investigations were focused on inorganic nanomaterials comprising of metals, metal oxides, nanocomposites and quantum dots. Herein, we provide an analysis of these findings, especially, considering the more recent developments in this new decade. We made an attempt to bring out the differences between chip-based as well as tubular continuous flow systems. We also cover, for the first time, various opportunities the tools from the field of computational fluid dynamics provide in designing LOC systems for synthesis inorganic nanomaterials. Particularly, we provide unique examples to demonstrate that there is a need for concerted effort to utilize LOC devices not only for synthesis of inorganic nanomaterials but also for carrying out superior in vitro studies thereby, paving the way for faster clinical translation. Even though LOC devices with the possibility to carry out multi-step syntheses have been designed, surprisingly, such systems have not been utilized for carrying out simultaneous synthesis and bio-functionalization of nanomaterials. While traditionally, LOC devices are primarily based on microfluidic systems, in this review article, we make a case for utilizing millifluidic systems for more efficient synthesis, bio-functionalization and in vitro studies of inorganic nanomaterials tailor-made for biomedical applications. Finally, recent advances in the field clearly point out the possibility for pushing the boundaries of current medical practices towards personalized health care with a vision to develop automated LOC-based instrumentation for carrying out simultaneous synthesis, bio-functionalization and in vitro evaluation of inorganic nanomaterials for biomedical applications.

Ligand‐Stabilized and Atomically Precise Gold Nanocluster Catalysis: A Case Study for Correlating Fundamental Electronic Properties with Catalysis

We present results from our investigations into correlating the styrene-oxidation catalysis of atomically precise mixed-ligand biicosahedral-structure [Au25(PPh3)10(SC12H25)5Cl2](2+) (Au25-bi) and thiol-stabilized icosahedral core-shell-structure [Au25(SCH2CH2Ph)18](-) (Au25-i) clusters with their electronic and atomic structure by using a combination of synchrotron radiation-based X-ray absorption fine-structure spectroscopy (XAFS) and ultraviolet photoemission spectroscopy (UPS). Compared to bulk Au, XAFS revealed low Au-Au coordination, Au-Au bond contraction and higher d-band vacancies in both the ligand-stabilized Au clusters. The ligands were found not only to act as colloidal stabilizers, but also as d-band electron acceptor for Au atoms. Au25-bi clusters have a higher first-shell Au coordination number than Au25-i, whereas Au25-bi and Au25-i clusters have the same number of Au atoms. The UPS revealed a trend of narrower d-band width, with apparent d-band spin-orbit splitting and higher binding energy of d-band center position for Au25-bi and Au25-i. We propose that the differences in their d-band unoccupied state population are likely to be responsible for differences in their catalytic activity and selectivity. The findings reported herein help to understand the catalysis of atomically precise ligand-stabilized metal clusters by correlating their atomic or electronic properties with catalytic activity.

Millifluidics for Time-resolved Mapping of the Growth of Gold Nanostructures

Innovative in situ characterization tools are essential for understanding the reaction mechanisms leading to the growth of nanoscale materials. Though techniques, such as in situ transmission X-ray microscopy, fast single-particle spectroscopy, small-angle X-ray scattering, etc., are currently being developed, these tools are complex, not easily accessible, and do not necessarily provide the temporal resolution required to follow the formation of nanomaterials in real time. Here, we demonstrate for the first time the utility of a simple millifluidic chip for an in situ real time analysis of morphology and dimension-controlled growth of gold nano- and microstructures with a time resolution of 5 ms. The structures formed were characterized using synchrotron radiation-based in situ X-ray absorption spectroscopy, 3-D X-ray tomography, and high-resolution electron microscopy. These gold nanostructures were found to be catalytically active for conversion of 4-nitrophenol into 4-aminophenol, providing an example of the potential opportunities for time-resolved analysis of catalytic reactions. While the investigations reported here are focused on gold nanostructures, the technique can be applied to analyze the time-resolved growth of other types of nanostructured metals and metal oxides. With the ability to probe at least a 10-fold higher concentrations, in comparison with traditional microfluidics, the tool has potential to revolutionize a broad range of fields from catalysis, molecular analysis, biodefense, and molecular biology.

Chemically Induced Magnetism in Atomically Precise Gold Clusters

Comparative theoretical and experimental investigations are reported into chemically induced magnetism in atomically-precise, ligand-stabilized gold clusters Au25 , Au38 and Au55 . The results indicate that [Au25 (PPh3 )10 (SC12 H25 )5 Cl2 ](2+) and Au38 (SC12 H25 )24 are diamagnetic, Au25 (SC2 H4 Ph)18 is paramagnetic, and Au55 (PPh3 )12 Cl6 , is ferromagnetic at room temperature. Understanding the magnetic properties resulting from quantum size effects in such atomically precise gold clusters could lead to new fundamental discoveries and applications.

X-Ray Absorption Near-Edge Structure (XANES) Spectroscopy Study of the Interaction of Silver Ions with Staphylococcus aureus, Listeria monocytogenes, and Escherichia coli

ABSTRACT Silver ions are widely used as antibacterial agents, but the basic molecular mechanism of this effect is still poorly understood. X-ray absorption near-edge structure (XANES) spectroscopy at the Ag LIII, S K, and P K edges reveals the chemical forms of silver in Staphylococcus aureus and Escherichia coli (Ag+ treated). The Ag LIII-edge XANES spectra of the bacteria are all slightly different and very different from the spectra of silver ions (silver nitrate and silver acetate), which confirms that a reaction occurs. Death or inactivation of bacteria was observed by plate counting and light microscopy. Silver bonding to sulfhydryl groups (Ag-S) in cysteine and Ag-N or Ag-O bonding in histidine, alanine, and dl-aspartic acid was detected by using synthesized silver-amino acids. Significantly lower silver-cysteine content, coupled with higher silver-histidine content, in Gram-positive S. aureus and Listeria monocytogenes cells indicates that the peptidoglycan multilayer could be buffering the biocidal effect of silver on Gram-positive bacteria, at least in part. Bonding of silver to phosphate groups was not detected. Interaction with DNA or proteins can occur through Ag-N bonding. The formation of silver-cysteine can be confirmed for both bacterial cell types, which supports the hypothesis that enzyme-catalyzed reactions and the electron transport chain within the cell are disrupted.

Lab-on-a-chip devices for gold nanoparticle synthesis and their role as a catalyst support for continuous flow catalysis

Abstract Lab-on-a-chip (LOC) systems are extensively used in recent times for applications in nanotechnology ranging from synthesis of nanomaterials to their utilization in catalysis, biomedicine, and drug delivery. A variety of nanomaterials – inorganic materials such as metal, metal oxide, quantum dots, and organic materials based on polymers and biological molecules – have been synthesized and their applications explored based on LOC devices. Among several inorganic nanomaterials, the applications of LOC devices for gold-based nanomaterials have been widely investigated over the past couple of decades. Though the synthesis and applications of inorganic nanomaterials using these systems have been thoroughly reviewed earlier, including those from our group, there are only a few recent review articles that cover gold-based nanomaterials. As the promise of supported gold nanoparticles (NPs) as exceptionally effective catalysts is beginning to be realized, LOC-based approach for continuous flow gold catalysis has begun to be exploited. Here, in this review, we focus on synthesis and catalysis applications of nanostructured gold using the LOC systems. With millifluidics-based LOCs gaining traction, this review fulfills the need for a comprehensive analysis covering both traditional microfluidics as well as recent millifluidics for catalysis applications utilizing gold nanomaterials.

Millifluidics for Chemical Synthesis and Time-resolved Mechanistic Studies

Procedures utilizing millifluidic devices for chemical synthesis and time-resolved mechanistic studies are described by taking three examples. In the first, synthesis of ultra-small copper nanoclusters is described. The second example provides their utility for investigating time resolved kinetics of chemical reactions by analyzing gold nanoparticle formation using in situ X-ray absorption spectroscopy. The final example demonstrates continuous flow catalysis of reactions inside millifluidic channel coated with nanostructured catalyst.

Understanding Au∼98Ag∼46(SR)60 nanoclusters through investigation of their electronic and local structure by X-ray absorption fine structure

Here we report the electronic and local atomic structure of thiol-stabilized Au∼98Ag∼46(SR)60 nanoclusters investigated by synchrotron radiation-based X-ray absorption fine structure (XAFS). Au L3-edge X-ray absorption near edge fine structure (XANES) was used to examine the d band character of Au, which is highly related to the electronic, magnetic and catalytic activities of Au. It was observed that the d band hole population of Au in Au∼98Ag∼46(SR)60 was higher than that of bulk Au. The formation of the AuAg alloy was confirmed by extended X-ray absorption fine structure (EXAFS). The EXAFS results also suggested that Au atoms in Au∼98Ag∼46(SR)60 nanoclusters preferred to occupy the metal core sites, while the Ag atoms were mainly on the surface.

The enigma of Au21(SC2H4Ph)14 nanocluster: a synthetic challenge

Abstract Recent investigations into atomically precise gold clusters show that not all magic-numbered clusters can be readily obtained through conventional synthetic routes. For example, Au21(SR)14, a magic-numbered cluster, was only obtained as a minor product from a mixture of clusters but was never synthesized in pure form using a single-step synthetic approach. We have made several attempts, albeit without any success, using a variety of approaches to synthesize Au21(SR)14 clusters in a single step. We show in this communication that synthetic failure is not likely due to electronic instabilities based on computational investigation of its electronic structure. Our DFT calculations show that the optimized cluster consists of a center Au13 core cluster capped by two Au2(SCH2CH3)3 fragments and four Au(SCH2CH3)2 fragments and is energetically stable. The findings reported here should give more confidence for the synthetic chemists to successfully synthesize Au21(SR)14 in the near future.